Friday, June 21, 2013

Cannabis and HIV


What is cannabis?

Cannabis, also known as marihuana, marijuana, pot, grass, bhang, charas, ganja, weed, and hashish is one of the so-called social or recreational drugs.  It is obtained from the flowering hemp plant Cannabis saliva



Pharmacologically, the principal psychoactive constituent of cannabis is the cannabinoid tetrahydrocannabinol (THC).  THC and other cannabinoids cross the blood brain barrier and act primarily on the cannabinoid 1 (CB1) receptors in the central nervous system affecting brain function.  This results in alterations in mood, perception, consciousness, cognition and behavior.  It also acts on the Cannabinoid 2 (CB2) receptors found primarily on cells of the immune system, gastrointestinal tract and peripheral nervous system.  CB2 does not mediate any of the psychoactive effects mentioned above.  There are three main types of cannabis products: herb (marijuana), resin (hashish) and oil (hash oil).  Cannabis herb comprises the dried and crushed flower heads and surrounding leaves. It often contains up to 5 per cent THC content. However, sinsemilla, derived from the unfertilized female plant, can be much more potent. Cannabis resin can contain up to 20 per cent THC content.  The most potent form of cannabis is cannabis oil, derived from the concentrated resin extract.  It may contain more than 60 per cent THC content.

How is cannabis consumed?  
  
It can be smoked (e.g. bongs and joints), snorted as a snuff, eaten (e.g. brownies and cannabutter), inhalation of vaporized herbal cannabis, drunk (e.g. tea and milk), topically (e.g. balms, lotions, waxes and bars),

Are there any medical uses for Cannabis relating to HIV infection? 

This is a difficult question to answer.  There are difficulties in researching the effects of cannabis.  Many people who smoke cannabis also smoke tobacco.  And users of cannabis often mix it with tobacco.  This can make it difficult to know whether it is the tobacco, the cannabis, or both that has caused a cancer.  The amount of THC in cannabis also varies.  Some of the cannabis available today is much stronger than it was 20 years ago.  These versions contain more THC.  Another difficulty researchers have is in recruiting people who smoke cannabis into studies. Because cannabis is an illegal drug in many countries, including the Philippines, people may be reluctant to take part in research. And if they do agree to take part, they may not say how much cannabis they actually smoke.  Thus it is very difficult to determine with certainty it’s long term effects or efficacy as a treatment for any medical condition.  In those countries in which it is used, it is important to stress that medical marijuana is a doctor-prescribed treatment and should only be used according to a doctor's instruction.  

Medical marijuana involves use of the cannabis extracts, called cannabinoids, secured from legal vendors, in a doctor-prescribed way for specific purposes. Medical use of marijuana can help relieve symptoms such as pain, glaucoma, migraine headaches, nausea, and weight loss.  However, due mostly to its legal status in many countries, it has not been thoroughly tested to find out how it interacts with many medications, foods, herbs, or supplements and therefore one should never self medicate with it.  
In 1996, a clinical trial in San Francisco found that people with HIV wasting syndrome who used cannabis were more likely to put on weight.  A study in 2007 found that HIV-positive users of the drug had relief from the symptoms of peripheral neuropathy. The drug is also widely used to relieve insomnia and the symptoms of anxiety and stress. It is also used by people with multiple sclerosis as a muscle relaxant.

While some studies have classified CB2 as a suppressor of CD4 cells and early trials indicated that marijuana use was associated with progression to AIDS, more recent analyses suggest that the drug isn’t associated with significant immune suppression. In fact, both smoked marijuana and Marinol (dronabinol the pharmaceutical formulation of THC used for loss of appetite associated with weight loss in patients with AIDS), have been associated with increases in CD4 cell counts—along with a decrease in viral load—but only in short-term studies and laboratory experiments.  The CB2 receptor, is a protein located on the surface of macrophages.  CB2 is a binding site for substances called cannabinoids, the primary active compounds of cannabis (marijuana), and it may play a role in blocking inflammation in the CNS.  To repeat, unlike its counterpart, the CB1 receptor, which is found primarily on neurons in the brain, CB2 does not mediate the psychoactive effects for which cannabis is popularly known.

The problem associated with its status as an illegal drug in any setting, including a medical one, can be seen in recent reports onto the possible future used of medical cannabis. 

1)  There has been much pharmacological interest in developing agents that selectively target CB2.  Ideally, these compounds would help limit chronic inflammatory responses and would not bind to CB1.  The most promising compounds are those derived from THC (tetrahydrocannabinol), the main active substance in cannabis.  The development of such drugs, however, hinges largely on knowing which cells harbor HIV. Earlier studies suggested that T cells, central components of the immune system, are HIV reservoirs. 

According to Ramirez and the study's senior investigator, Yuri Persidsky, MD, PhD, Chair of the Department of Pathology and Laboratory Medicine at TUSM, macrophages likely are the primary reservoir for HIV.  They are among the first cells to become infected following sexual transmission of the virus, and they are found in every organ of the human body and circulate in the blood.  It is currently thought that macrophages may be responsible for introducing HIV into the brain, ultimately initiating HIV-associated cognitive decline.  Using a non-clinical HIV macrophage cell model, they began by treating the HIV-infected cells with one of three different synthetic CB2-activating compounds. The cells were then sampled periodically to measure the activity of an enzyme called reverse transcriptase, which is essential for HIV replication. After seven days, the team found that all three compounds had successfully attenuated HIV replication.  The results suggest that selective CB2 agonists could potentially be used in tandem with existing antiretroviral drugs, opening the door to the generation of new drug therapies for HIV/AIDS. The data also support the idea that the human immune system could be leveraged to fight HIV infection. “Our study suggests that the body’s own natural defenses can be made more powerful to fight some of the worst symptoms of HIV,” Persidsky explained.  He also noted that stimulating CB2 receptors in white blood cells could produce similar benefits against other viral infections.

2)  CR2 has also been found on a variety of immune system cells and is present on CD4 cells in abundance.  In effect, the mechanisms by which the interactions between THC and the cannabinoid receptors alter CD4 cell function remain unclear. One particular area of interest, though, is the connection between CR2 and CXCR4, another receptor on immune system cells. For example, CR2 activation blocks CXCR4 from directing the movement of certain cells in the body (chemotaxis). CR2 also plays a role in moving white blood cells out of bone marrow (egress), a role previously attributed largely to CXCR4.  The apparent “cross talk” between CR2 and CXCR4, therefore, led the Mt. Sinai researchers—under the direction of Cristina Maria Costantino, PhD—to explore whether stimulation of CR2 can block the way CXCR4 interacts with a particular form of HIV: CXCR4-tropic virus.  during the early years of untreated HIV infection, HIV primarily targets—or is tropic for—cells with the CCR5 receptor. As HIV disease progresses, however, approximately 50 percent of people living with HIV see their virus develop preference for the CXCR4 receptor on CD4 cells. This particular form of the virus, research has shown, is associated with rapid disease progression although it is unclear if the emergence of CXCR4-tropic virus is a cause or an effect of immune suppression.  Costantinos test tube experiments proved encouraging. Using a cannabinoid receptor agonist—a THC-like compound—her team found that activation of CR2 inhibited CXCR4-tropic HIV infection. It did this, not by altering the number of CXCR4 receptors on CD4 cells—this is a therapeutic approach being explored by others—but rather by blocking the receptor’s “signaling process” and interaction with HIV. 

What is the effect/risk of cannabis on an HIV+ person?

Like all uncontrolled street drugs adulterants have frequently been found in cannabis.  Chalk (in the Netherlands) and glass particles (in the UK) have been used to make cannabis appear to be higher quality.  Increasing the weight of hashish products in Germany with lead caused lead intoxication in at least 29 users   In the Netherlands two chemical analogs of Viagra were found in adulterated marijuana.

According to both the "Talk to FRANK" website and the UKCIA website, Soap Bar, "perhaps the most common type of hash in the UK", was found "at worst" to contain turpentine, tranquilizers, boot polish, henna and animal feces.  One small study of five "soap-bar" samples seized by UK Customs in 2001 found huge adulteration by many toxic substances, including soil, glue, engine oil and animal feces.  Even if the product you are buying is free from adulterants or you grow your own, it is impossible to be certain exactly how much of each particular compound within the product you are self administering.  The whole plant contains many compounds, which have different actions in the human body. For example, studies show that THC can raise anxiety and cause paranoia, while cannabidiol (CBD) may reduce them. Components of the whole plant can have nearly opposite effects in the human brain, so that one compound can change the effects of another.

Smoking or eating whole marijuana can cause a number of mental and emotional effects, including feelings of euphoria, short-term memory loss, difficulty in completing complex tasks, changes in the perception of time and space, sleepiness, anxiety, confusion, and inability to concentrate.  A small but significant percentage of people in medical studies didn’t like the mental effects and withdrew from studies because of them. In studies, cannabinoids have been linked with effects such as depression, paranoia, and hallucinations. Those with a genetic vulnerability to mental illness may have more serious mental and emotional effects from marijuana use such as schizophrenia, psychosis, depersonalization disorder and depression.

Physical side effects include low blood pressure, fast heartbeat, dizziness, slow reaction time, and heart palpitations. Instances of serious heart problems are very rare.
Many researchers agree that marijuana smoke contains known carcinogens, or chemicals that can cause cancer much like those in tobacco smoke. Studies have shown changes in the linings of the breathing passages in marijuana smokers.  But results of epidemiologic studies of marijuana and cancer risk have been inconsistent, and most recent epidemiologic studies have not found a substantial effect on cancer risk.  It’s possible that some of these differences are due to the fact that most marijuana smokers don’t smoke as much or as often as tobacco smokers.  Effects might be more evident in heavy marijuana smokers.  

Some researchers also caution that these studies are difficult to conduct, as some people may not admit to illegal habits such as smoking marijuana, and that negative results should not be interpreted as convincing evidence of safety.  Most researchers believe herbal marijuana contains toxins and carcinogens that lead to increased risk of respiratory diseases and cancer and therefore recommend other methods of consumption of medical marijuana besides smoking.  It should be noted that people inhale cannabis smoke for longer than cigarette smoke. This is to get the full effect of the cannabis. But it means that the smoke is in contact with the lungs for longer.  Various researchers have found that smoking marijuana may cause lung disease and increase the risk of cancer of the lungs, mouth, tongue and testicles.   

It is not known how cannabis reacts with ARVs.  A small American study found that cannabis use did not impact on the effectiveness of the protease inhibitor Indinavir even though the drugs use the same mechanism to pass through the body.

Like any mood and consciousness-altering drug, cannabis may have an impact on a HIV+ persons ability to adhere to their ARV and other medication schedules.   People planning to use cannabis, or any other recreational drug, and thus risk arrest as well as the unwanted side effects of the drug, may need to develop strategies to help them take their medication at the right time and in the right way.

Overwhelmingly the evidence suggests that, until medical marijuana is available as a controlled substance under that supervision of a qualified Medical Practitioner, its use should be avoided.

I hope people have found this post useful.

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Get tested, stay healthy and, if you’re HIV+, compliant with your ARV regimen,

Malcolm Brown.
International Contributor






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